Autism Origins Explored: A Deep Dive into Genetics, Environment, and Debunked Myths

Overview: This article explores genetic and environmental factors that are believed to contribute to autism disorder, as well as factors that have been erroneously said to but do not contribute to the disorder.

 Introduction

Spoiler alert ~ there is no one cause of autism. Believe me, I’ve looked and there is no such definitive explanation for how or why this condition occurs. That being said, scientists have made tremendous strides over the last couple of decades in identifying factors that contribute to autism spectrum disorder. This article synthesizes the decades of research and current understanding of factors that contribute to this complex disorder.

There are two primary contributors to the formation of autism spectrum disorder - , genetics and environment. Genetics refers to the biological building blocks that are passed down to us through birth. Genes are why I blame my father for losing my hair before I turned 30. Environmental factors are the things outside of our genes that contribute to growth. An example of an environmental factor is stress, and stress is why my father tells me that it’s my fault that my hair fell out and not his. In reality, my hair loss is likely due to a combination of both genes (men in my family tend to lose their hair), and environment (I tend to internalize stress and do not always practice the best selfcare). Similarly, the most informed hypothesis on the cause of autism is that it is likely caused by a combination of genetic and environmental factors.

Genetics

Research on the genetic contributions to autism is on-going and this article is not meant to be an exhaustive discussion of the literally hundreds of genes that have been suggested to play a role in the diagnosis. This article is a summary of some of the most prominent research and its implications. Please note that I am not a geneticist and have never played one on TV. If you are looking for more “scientific” discussions on this topic I have included a list of references that you may want to explore if you are not satisfied with my infantile summarizing.

Autism was once believed to be completely environmentally based. In 1977, researchers Folstein and Rutter found a significantly increased likelihood of the disorder among siblings and twins. This was a seminal point in understanding the causes of autism, as it showed that genetics certainly play a role in its development. Since then, theories have ping-ponged between which factor, genes or environmental, play the larger role in formation of the disorder (Hallmayer et al. 2011; Colvert, et al. 2015). Given the unsettled status of the research, I will not attempt to define which factor is more influential and instead discuss how each factor impacts autism development differently. If you seek definitive ratios, I refer you to the geek squads referenced below.

Improvements in genetic screening and sequencing have been a boon for autism research in the 21st century. Scientists have unearthed hundreds of “risk genes” that may contribute to autism development. Again, because this is a summary, my focus here is on broader categories of genes rather than specific genes. One such category is the genes that foster “synapse formation” in the brain. A synapse is a gap between neurons in the brain that allows signals to flow from one part of the brain to another. There are many genes that contribute to synapse formation, and researchers have discovered that people with autism tend to have genes that have altered some of these synapses so that the brain takes on a different structure (Rylaarsdam & Guemez-Gamboa, 2019). This seems to be one prominent contributor to autism development.

Monogenic causes of autism – or causes that are attributable to only one gene – can be difficult to discern. Researchers and doctors must determine whether disorders resulting from one altered gene are indeed autism, or their own unique genetic disorder. The most common monogenic cause of autism is what is known as Fragile X Syndrome (Simberlund et al. 2019). This genetic syndrome impacts learning, communication skills, physical development, and sensory sensitivity. If this sounds familiar it is because 60% of people with Fragile X Syndrome also qualify for an autism diagnosis (Roberts et al. 2020). Whether Fragile X Syndrome and autism are independent but similar diagnoses, or the same diagnosis but with different causes is up to considerable debate in the scientific community.

Another genetic factor that is increasingly seen as a contributor to autism is “somatic mosaicism” caused by DNA mutations that occur after egg fertilization. As you may recall from high school biology, the zygote (fertilized egg) that becomes a person is a combination of DNA from the sperm and the egg. The combined DNA typically play well together and form the new DNA of the child. Not so in cases of somatic mosaicism where there is a simultaneous increase of maternal and paternal DNA in the brain. This can have a pathogenic effect and lead to genetic mutations that may then contribute to the development of autism and other neurodevelopmental disorders (Lim et al., 2017). Interestingly, somatic mosaicism-caused genetic variations often impact the amygdala (Rasia-Filho, Londero, and Achaval, 2000), the part of the brain that is critical for emotional response and social awareness.

Other genetic mutations that are suspected to contribute to the development of autism have to do with “neuronal migration.” During a person’s development, the brain, and the neurons that it is made of, move into place over time. The brain does not develop instantaneously, but rather grows over time as neurons move into place to form the different structures that make up the brain. Researchers have found that people with autism, as well as multiple other disorders, experience unique genetic changes at the earliest stages of that neuronal migration (Pan, Wu, & Yuan, 2019). This result is alterations in parts of the brain that may contribute to the development of autism.

While there are many research paths exploring how genetics may contribute to autism, the above examples capture the basic principles of how a person’s genetics can foster the disorder. Given that genes are passed down from generation to generation, it stands to reason that a person with a family history of autism would have a greater likelihood of having an autistic child. After all, genes are the building blocks of life, and slight variations in these genes may impact how a person develops. When those genetic variations impact the developing brain, the individual may be more susceptible to autism.

Environmental Factors

While there is a growing body of evidence that genes play a significant role in the development of autism, this does not exclude the possibility of a synergistic effect with the genetics and environmental factors that may increase the prevalence of the disorder. Many of these environmental factors occur in-utero and cannot be easily controlled, but understanding the factors is nonetheless important in our quest to understand the phenomena of autism.

Parental age has long been assumed to be a contributing environmental factor to the likelihood of autism development. Studies have shown that older parents have an increased likelihood of having a child with autism (Janecka et al., 2019; Wu et al., 2017). This research suggests that there may be up to a 18% increase in autism development for every added decade of parental age. It was once thought that these effects were only true with advanced maternal age, but studies suggest that both maternal and paternal age play a role in the development of autism.

There is additional evidence to suggest that maternal infection while a child is in-utero can increase the likelihood of autism. A recent meta-analysis found that infection – specifically one that requires maternal hospitalization – can increase the likelihood of a child developing autism by up to 12% (Jiang et al., 2016). It is believed that fetal exposure to pathogens, or the inflammatory impact of maternal illness, may cause the increased susceptibility. The impacts seem to be particularly present with maternal bacterial infections requiring multiple hospitalizations. (Zerbo et al., 2015).

In utero exposure to certain chemicals has also been associated with the development of autism. Valproic acid, a medication for epilepsy, is suspected to contribute to autism (Taleb, 2021), but the data is thus far inconclusive. One recent study found observable autism phenotypes in mice that were exposed to valproic acid (Mitsuhashi et al, 2023). The effects of increased autism are not just a result of chemicals ingested by the mother. In fact, there is evidence that exposure to high levels of air pollution can also contribute to autism development (Imbriani et al., 2021). Research on in utero chemical exposure is in its infancy (excuse the pun), but the research is developing (again, excuse the pun) and the growing body (ugh) of evidence suggests that exposure to certain chemicals at different stages of in utero development can increase the likelihood of developing autism.

Another potential environmental contributor to autism that is newly being researched has to do with a mother’s autoantibodies. Dr. Judy Van de Water from UC Davis has explored how a fetus whose mother has an autoimmune disorder may have their development impacted by disruptions from the mother’s autoantibodies (Jones & Van de Water, 2019). This research is on-going and appears as though it only impacts a small percentage of developing fetuses, but it is another example of how early disruptions in brain development may contribute to autism.

The range of research into autism-influencing environmental factors is wide and varied. It is important to note that none of these factors have been shown to be singularly causal – in that these factors do not “cause” autism on their own. The research seems to show that environmental factors have the biggest impact in utero, which suggests that by the time a child is born their brain is already developed in a way where autism will or will not be present. Although not solely responsible for the condition, it does appear that environmental factors may push a genetically predisposed fetus towards the development of a disorder. Much like my baldness, the environmental factors just pushed the genetic factors to be more pronounced.

Factors with No Effect on the Development of Autism

A discussion of the potential causes of autism would be incomplete if we do not also consider some of the many factors that do not contribute to the development of autism. There have been many suspected factors over the years that have been thoroughly researched and ruled out as having a causal relationship to the disorder. Unfortunately, many influencers in popular culture ignore the research and continue to “blame” the factors and lead people to avoid certain exposures that are in fact perfectly healthy.

The most obvious example of lingering belief in the inaccurate cause of autism is the use of vaccines – specifically the vaccine for measles, mumps, and rubella (MMR). This erroneous belief started in 1998, when a British doctor named Andrew Wakefield wrote an article in The Lancet claiming that compounds in the MMR vaccine caused autism. Decades of research assessing hundreds of thousands of people have disproved his claim (Institute of Medicine, 2012; Nordahl et al., 2011; Demicheli et al. 2013), and the article was eventually rescinded. Dr. Wakefiled even lost his medical license. Yet there are members of society who continue to believe the myth and distrust the vaccine.

Vaccines are not the only medical interventions that have been incorrectly suggested to cause autism. It was also once believed that maternal use of antidepressants such as SSRIs while pregnant lead to increased rates of autism; however, Kaplan et al. (2016) and other studies have found that mothers using SSRIs have autistic kids at the same rate as mothers with untreated mental health issues. Similarly, it was once posited that having the flu, or getting a flu shot while pregnant caused heightened levels of autism, but research by Zebro et al. (2016) and others have found no such correlation.

The world of autism research is constantly changing, and our understanding of the causes of this complex disorder will change with it. When considering different studies, it is important to consider whether the research was peer-reviewed, had a randomized approach, and whether the researchers had any conflicts of interest. These factors do not guarantee that the research is accurate, but they are critical components to the best possible science. It is a tragedy for a well-meaning person to avoid safe and beneficial medical treatment, such as antidepressants or vaccines, based on inaccurate speculation.

Summary

Autism spectrum disorder is a complex, neurodevelopmental condition that scientists are still working to understand. Given the relatively novel science of genetic sequencing and screening, it is hard to conclusively determine the impact, if any, of each genetic variation. However, as more studies are completed it seems clear that the genes that impact brain development in utero may contribute to the development of autism. When these genetic issues combine with environmental stressors it appears even more likely that a fetus will develop in a way that can lead to autism. While these environmental factors may not be necessarily causal, it does appear as though they can tip the scales.

It is an understandably difficult and highly personal process to contemplate the genetic and environmental factors that could impact an individual or family. While there is not and may never be a concrete answer for a diagnosis, the goal of this article is to ensure that inquiring minds have the most current and best information about potential causes of autism disorders.

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